Tissue resulting from wound repair, commonly known as scar tissue, is visibly distinct from normal tissue and is generally conceded to be deficient in the elastic fiber component normally present in skin, blood vessels, and related tissue. Previous investigations into the structure of elastic fibers present in blood vessel walls and other elastic materials, such as ligaments, present in humans and animals, has given some insight into the structure of these elastic fibers. The connective tissue of vascular walls is formed from two principal types of protein. Collagen, the principal proteinaceous component of connective tissue, forms the strength-giving structure. In the vascular wall, and particularly in its internal elastic lamina, collagen is associated with natural elastic fibers formed from a different protein, known as tropoelastin. In the relaxed vascular wall, the collagen fibers tend to be folded or crimped, and the elastic fibers are in their retracted state. On distension or stretching, the elastic fibers stretch out, and, as their extension limit is approached, the collagen fibers come into tension to bear the load. As the load diminishes, the elastic fibers draw the wall back to its original dimensions and the collagen fibers back into their folded state. In a synthetic vascular material of the types currently available, such as Dacron, the weave can be viewed as providing the structural analogue of folded collagen, but there is no true elastomeric component.
The central portion of the elastic fibers of vascular wall, skin, lung and ligament is derived from a single protein called tropoelastin. Polypeptide sequences of tropoelastin from vascular wall have been shown by Sandberg and colleagues to contain a repeat hexapeptide (Ala-Pro-Gly-Val-Gly-Val).sub.n, a repeat pentapeptide (Val-Pro-Gly-Val-Gly).sub.n, and a repeat tetrapeptide (Val-Pro-Gly-Gly).sub.n where Ala, Pro, Val and Gly respectively represent alanine, proline, valine and glycine amino acid residues. Peptide representations in this application conform to the standard practice of writing the NH.sub.2 -terminal amino acid residue at the left of the formula and the CO.sub.2 H-terminal amino acid residue at the right. Likewise, the amino acid sequence in the vicinity of natural crosslinks of tropoelastin is known, as disclosed in Gray et al., Nature, 246, 461-466 (1973). A high polymer of the hexapeptide has been synthesized, whereby it forms cellophane-like sheets. The hexapeptide was therefore thought to fill a structural role in the natural material. Synthetic high polymers of the pentapeptide and of the tetrapeptide, on the other hand, are elastomeric when cross-linked and appear to contribute to the functional role of the elastic fiber. For example, the chemically cross-linked polypentapeptide can, depending on its water content and degree of crosslinking, exhibit the same elastic modulus as native aortic elastin.
A synthetic polypentapeptide based on the pentapeptide sequence discussed above was disclosed and claimed in U.S. Pat. No. 4,187,852 to Urry and Okamoto. A composite bioelastic material based on an elastic polypentapeptide or polytetrapeptide and a strength-giving fiber was disclosed and claimed in U.S. Pat. No. 4,474,851 to Urry. A bioelastic material having an increased modulus of elasticity formed by replacing the third amino acid in a polypentapeptide with an amino acid of opposite chirality was disclosed and claimed in U.S. Pat. No. 4,500,700 to Urry. Pending patent applications in this area (both indicated to be allowable) are Ser. No. 533,670, now U.S. Pat. No. 4,605,413 directed to a chemotactic peptide and Ser. No. 533,524, now U.S. Pat. No. 4,589,882 directed to an enzymatically cross-linked polypeptide.
However, there continues to be a need for bioelastic materials based on the polypentapeptide and polytetrapeptide repeating sequences having modified chemical and biological characteristics.